Signal transducer and activator of transcription factor 3 (STAT3), a member of the STAT transcription factor family, plays a key role in various biological processes including inflammation embryonic development and tumorigenesis. Previous work in our laboratory showed that STAT3 is expressed in myoblasts and regulates myoblast proliferation and differentiation in an in vitro cell culture model. However, it remains unclear whether STAT3 regulates muscle satellite cells (i.e., muscle stem cells) in vivo. In this study, we took advantage of the Cre/loxP system and deleted STAT3 specifically in Pax7-positive muscle precursor cells. By further interbreeding the STAT3 conditional knock-out mice (cKO) with the mdx mice (i.e., the mouse model for the Duchenne muscular dystrophy), we also obtain...[ Read more ]

Signal transducer and activator of transcription factor 3 (STAT3), a member of the STAT transcription factor family, plays a key role in various biological processes including inflammation embryonic development and tumorigenesis. Previous work in our laboratory showed that STAT3 is expressed in myoblasts and regulates myoblast proliferation and differentiation in an in vitro cell culture model. However, it remains unclear whether STAT3 regulates muscle satellite cells (i.e., muscle stem cells) in vivo. In this study, we took advantage of the Cre/loxP system and deleted STAT3 specifically in Pax7-positive muscle precursor cells. By further interbreeding the STAT3 conditional knock-out mice (cKO) with the mdx mice (i.e., the mouse model for the Duchenne muscular dystrophy), we also obtained a Stat3-/-:mdx double knock-out (dKO) mouse line. Although the satellite cell number in the cKO mice did not seem to greatly differ from that of the wild type controls, the regeneration potential of cKO mice was impaired and the size of the regenerating muscle fibers was reduced in a cardiotoxin-induced muscle regeneration model. Moreover, the adult dKO mice displayed more severe muscular dystrophy compared with the mdx mice, which was evidenced by the reduced body size and muscle weight, increased fibrosis, and increased infiltration of inflammatory cells. We also found that Stat3-/- myoblasts had decreased proliferation rate, and accelerated differentiation potential. In addition, there was decreased Pax7 expression in Stat3-/- muscle satellite cells. So far, our work has demonstrated that STAT3 is involved in regulating muscle satellite cells in vivo in a cell-autonomous manner. We are now planning to perform both Stat3 ChIP-sequencing and RNA-sequencing experiments using Pax7-positive muscle satellite cells in order to understand the detailed molecular mechanisms by which STAT3 exert its functions in muscle satellite cells.